Aft2, a Novel Transcription Regulator, Is Required for Iron Metabolism, Oxidative Stress, Surface Adhesion and Hyphal Development in <i>Candida albicans</i>

Abstract

<div><p>Morphological transition and iron metabolism are closely relevant to <i>Candida albicans</i> pathogenicity and virulence. In our previous study, we demonstrated that <i>C. albicans</i> Aft2 plays an important role in ferric reductase activity and virulence. Here, we further explored the roles of <i>C. albicans</i> Aft2 in numerous cellular processes. We found that <i>C. albicans</i> Aft2 exhibited an important role in iron metabolism through bi-directional regulation effects on iron-regulon expression. Deletion of <i>AFT2</i> reduced cellular iron accumulation under iron-deficient conditions. Furthermore, both reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity were remarkably increased in the <i>aft2Δ/Δ</i> mutant, which were thought to be responsible for the defective responses to oxidative stress. However, we found that over-expression of <i>C. albicans AFT2</i> under the regulation of the strong <i>PGK1</i> promoter could not effectively rescue <i>Saccharomyces cerevisiae aft1Δ</i> mutant defects in some cellular processes, such as cell-wall assembly, ion homeostasis and alkaline resistance, suggesting a possibility that <i>C. albicans</i> Aft2 weakened its functional role of regulating some cellular metabolism during the evolutionary process. Interestingly, deletion of <i>AFT2</i> in <i>C. albicans</i> increased cell surface hydrophobicity, cell flocculation and the ability of adhesion to polystyrene surfaces. In addition, our results also revealed that <i>C. albicans</i> Aft2 played a dual role in regulating hypha-specific genes under solid and liquid hyphal inducing conditions. Deletion of <i>AFT2</i> caused an impaired invasive growth in solid medium, but an increased filamentous aggregation and growth in liquid conditions. Moreover, iron deficiency and environmental cues induced nuclear import of Aft2, providing additional evidence for the roles of Aft2 in transcriptional regulation.</p></div

    Similar works